TCL-1 and MTCP-1 are members of a novel family of human genes that are involved in T-ell malignancies and lymphoid proliferation and/or survival. These genes code for proteins of about 14 kDa molecular weight, that share 41% identical amino acid residues. Human TCL-1 and MTCP-1 and mouse TCL-1 have been expressed in E. coli and purified in milligram quantities for structural analysis. The crystal structure of MTCP-1 has been determined at 2.0 A resolution. The structure is a unique 8-stranded beta barrel with one short helix. The structure of TCL- 1 is very similar with a root mean square deviation of 1.7 angstrom on all common Calpha atoms. The structural information is being used for site- directed mutagenesis, and to design peptide analogs of surface regions of the proteins as potential inhibitors of oncogene function. Mutant forms of TCL-1 and MTCP-1 will be expressed, characterized and analyzed structurally in comparison to the wild type protein. Interacting proteins and other potential ligands of TCL-1 and MTCP-1 will be studied by crystallography and biochemical methods. The structures and functions of TCL-1 and MTP-1 proteins will be compared. Inhibitors of TCL-1 and MTCP-1 have potential for treatment for low-grade T-cell lymphomas and leukemias.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Program Projects (P01)
Project #
Application #
Study Section
Special Emphasis Panel (ZCA1)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Thomas Jefferson University
United States
Zip Code
Thompson, Lorraine H; Whiston, Roy A; Rakhimov, Yerzhan et al. (2010) A LIF/Nanog axis is revealed in T lymphocytes that lack MARCH-7, a RINGv E3 ligase that regulates the LIF-receptor. Cell Cycle 9:4213-21
Almanza, Gonzalo; Fernandez, Antonio; Volinia, Stefano et al. (2010) Selected microRNAs define cell fate determination of murine central memory CD8 T cells. PLoS One 5:e11243
Garzon, Ramiro; Liu, Shujun; Fabbri, Muller et al. (2009) MicroRNA-29b induces global DNA hypomethylation and tumor suppressor gene reexpression in acute myeloid leukemia by targeting directly DNMT3A and 3B and indirectly DNMT1. Blood 113:6411-8
Ghosh, Asish K; Shanafelt, Tait D; Cimmino, Amelia et al. (2009) Aberrant regulation of pVHL levels by microRNA promotes the HIF/VEGF axis in CLL B cells. Blood 113:5568-74
Pufnock, Jeff S; Rothstein, Jay L (2009) Oncoprotein signaling mediates tumor-specific inflammation and enhances tumor progression. J Immunol 182:5498-506
Croce, Carlo M (2009) Causes and consequences of microRNA dysregulation in cancer. Nat Rev Genet 10:704-14
Volinia, Stefano; Mascellani, Nicoletta; Marchesini, Jlenia et al. (2008) Genome wide identification of recessive cancer genes by combinatorial mutation analysis. PLoS One 3:e3380
Garzon, Ramiro; Garofalo, Michela; Martelli, Maria Paola et al. (2008) Distinctive microRNA signature of acute myeloid leukemia bearing cytoplasmic mutated nucleophosmin. Proc Natl Acad Sci U S A 105:3945-50
Garzon, Ramiro; Volinia, Stefano; Liu, Chang-Gong et al. (2008) MicroRNA signatures associated with cytogenetics and prognosis in acute myeloid leukemia. Blood 111:3183-9
Tili, Esmerina; Michaille, Jean-Jacques; Cimino, Amelia et al. (2007) Modulation of miR-155 and miR-125b levels following lipopolysaccharide/TNF-alpha stimulation and their possible roles in regulating the response to endotoxin shock. J Immunol 179:5082-9

Showing the most recent 10 out of 60 publications